The objective of this project is to study the developmental biology and molecular interaction of human pathogenic Leishmania in phlebotomine sand flies, and to determine the biological potential of these host-parasite associations in disease transmission. The ultrastructural morphology and developmental sequence of parasites in the sand fly gut, as well as attachment mechanisms to gut linings will be compared in natural and unnatural hosts. The role of the peritrophic membrane in influencing sand fly susceptibility to Leishmania will be studied, including membrane formation, fine structure, interaction with parasites, and chemical composition. The cytochemistry of the sand fly gut will be investigated to help elucidate whether or not parasite interaction with epithelial linings is lectin-mediated. Lectins will be isolated from the gut epithelium and characterized. The carbohydrate composition of microvillar- and cuticle-lined surfaces of the gut will be compared in refractory and susceptible sand fly hosts. The possible inhibitory effects of specific carbohydrates and lectins on parasite attachment, multiplication, and morphogenesis in the sand fly gut will be studied in vitro and in vivo. Methodology to be used in this research project includes experimental infection of sand flies, histology and histochemistry, light and transmission electron microscopy, electron microscopic cytochemistry, and biological assays.